Modulatory effect of bradykinin on the release of noradrenaline from rat isolated atria

Abstract
1 We investigated the modulation by bradykinin (BK) of electrically induced noradrenaline release in rat isolated atria preincubated with [3H]-noradrenaline. 2 BK (1-100nM) enhanced significantly the stimulation-induced outflow of radioactivity in a concentration-dependent manner with a calculated EC50 of 0.58 nM. 3 Des-Arg9-BK (0.1-100nM), a selective B1 receptor agonist, did not modify the stimulation-induced outflow of radioactivity. Hoe 140 (10 nM), a selective B2 receptor antagonist, but not [Leu8]-des-Arg9-BK (100 nM), a selective B1 receptor antagonist, blocked the facilitatory effect of BK. 4 The effect of BK was not affected by diclofenac (1 μm), a cyclo-oxygenase inhibitor. Bisindolyl-maleimide (1 μm), a protein kinase C inhibitor, significantly reduced the facilitatory effect of BK (10 nM), angiotensin II (0.3 μm) and phorbol dibutyrate (0.1 and 1 μm) but not of fenoterol (1 μm). 5 The results suggest that BK enhances noradrenaline release via a prejunctional B2 kinin receptor in the rat atrium. The effect appears to involve protein kinase C as a second messenger.